Papillary thyroid carcinoma (PTC) is the most common thyroid cancer, accounting for about 80% of all thyroid cancers. Although PTCs are usually curable with standard surgical and adjuvant radioiodine treatment, neck lymph node metastases are found in 30-65% of cases at initial diagnosis (1-3). Lymph nodes are the most frequent site of PTC metastasis and, if found, predict recurrence and poor survival (20). It is the presence of these and more distant metastases that are generally are the cause of death from the cancer, rather than the invasion of the primary tumors, themselves. Because lymph node metastases are often difficult to detect by eye, such metastases can be missed by current technologies, particularly at early stages of metastasis. Furthermore, lymph node metastases have been identified in the absence of a clinically detectable primary tumor. It would be beneficial to have an earlier and more accurate detection of lymph node metastases, so that patients having such metastases could be treated aggressively, whereas patients not exhibiting such metastases could be spared the adverse effects of such toxic treatments. Moreover, an assay for the presence of lymph node metastases could be used to detect recurrence of PTC, to follow the course of PTC, or to monitor the effectiveness of a treatment regimen for PTC. Such an assay would help improve individualized treatment for this cancer.
Several groups have performed expression profile analysis of metastatic primary PTC or in vitro model systems to identify clinical outcome markers (5, 6). Although these approaches might identify useful prognostic markers, they do not directly identify gene expression changes that occur in the metastatic cells. Identification of genes that are consistently expressed in metastatic PTC cells could yield useful biomarkers, which could be useful not only for prognosis, but also to identify occult metastatic cells in lymph node biopsies, etc. In addition to the practical uses as markers, genes associated with metastasis could help reveal the molecular mechanisms of the metastatic process.